Department of Pharmacology and Nephrology, University of Mississippi Medical Center, Jackson, Mississippi.

3

Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi; and bgrayson@umc.edu.

Abstract

Individuals that suffer injury to the spinal cord can result in long-term, debilitating sequelae. Spinal cord-injured patients have increased risk for the development of metabolic disease, which can further hinder the effectiveness of treatments to rehabilitate the cord and improve quality of life. In the present study, we sought to understand the impact of high-fat diet (HFD)-induced obesity on spinal cord injury (SCI) by examining transcriptome changes in the area of the injury and rostral and caudal to site of damage 12 wk after injury. Adult, male Long-Evans rats received either thoracic level contusion of the spinal cord or sham laminectomy and then were allowed to recover on normal rat chow for 4 wk and further on HFD for an additional 8 wk. Spinal cord tissues harvested from the rats were processed for Affymetrix microarray and further transcriptomic analysis. Diverse changes in gene expression were identified in the injured cord in genes such as MMP12, APOC4, GPNMB, and IGF1 and 2. The greatest signaling changes occurred in pathways involved in cholesterol biosynthesis and immune cell trafficking. Together, the cord changes in the chronically obese rat following thoracic SCI reveal further potential targets for therapy. These could be further explored as they overlap with genes involved in metabolic disease.

Paradigm used for the study. A: male rats received a sham-laminectomy or thoracic spinal contusion injury (tSCI) followed by 4 wk of recovery and placement on a palatable high-fat diet (HFD) for 8 wk. B: diagram of the dissections for cervical, thoracic, and lumbar regions. Microarray was performed on the thoracic region. Validation was performed on cervical, thoracic, and lumbar regions.

Quantitative (q)PCR validation of the microarray data of upregulated genes using RNA from the thoracic region and also up- and downstream to the injury site in the cervical and lumbar regions. n = 4–5/group, gray area demarcates the region of the injury. *P < 0.05, **P < 0.01, ***P < 0.001. Data are presented as means ± SE.

qPCR validation of the microarray data of downregulated genes using RNA from the thoracic region and also up- and downstream to the injury site in the cervical and lumbar regions. n = 4–5/group, gray area demarcates the region of the injury. *P < 0.05, **P < 0.01, ***P < 0.001. Data are presented as means ± SE.